general chapter 5.2.12. raw materials of biological origin ... · 03/02/2017 2 general chapter...

03/02/2017

1

General Chapter 5.2.12.

Raw materials of biological origin for the production of cell-based and

gene therapy medicinal products

Celine Pugieux-Amarantos, PhD

Scientific Assistant, European Pharmacopoeia Department

Celine PUGIEUX-AMARANTOS ©2017 EDQM, Council of Europe. All rights reserved.1

European Pharmacopoeia Training Session on Biologicals7-8 February 2017, Strasbourg

General Chapter 5.2.12 Regulatory frameworkRaw materials of biological origin for the production of cell-based and gene therapy medicinal products

Directive 2001/83/EC


03/02/2017

2


Directive 2001/83/EC - Annex I Part IV: legal definition of ATMPs


A biological medicinal product is a product, the active substance of which is a biological substance. A biological substance is a substance that is produced by or extracted from a biological source and that needs for its characterisation and the determination of its quality a combinationof physicochemical-biological testing, together with the production process and its control.

The following shall be considered as biological medicinal products: (…); advanced therapymedicinal products as defined in Part IV of this Annex.

Any other substances used for manufacturing or extracting the active substance(s) but fromwhich this active substance is not directly derived, such as reagents, culture media, foetal calf serum, additives, and buffers involved in chromatography, etc. are known as raw materials.



Pharmacovigilance for ATMPs

Directive 2002/98/EC

Human blood and blood components

EU Draft guideline GMP for ATMPs

Others

EMA reflection paper on

classification of ATMPs

Directive 2006/17/ECDonation,

procurement, and testing of human tissues and cells

Regulation 1394/2007

Advanced therapy medicinal products

EuropeanPharmacopoeia

(Ph.Eur.)

EMA Guideline on human cell-

based medicinal products

Directive 2001/83/EC - Annex I Part IV: legal definition of ATMPs

03/02/2017

3

General Chapter 5.2.12 Regulatory framework: Ph. Eur.Raw materials of biological origin for the production of cell-based and gene therapy medicinal products

5.14 Gene transfer medicinal products for human use

Chapter for information




Human haematopoietic stem cells (2323)


03/02/2017

4



Human haematopoietic stem cells (2323)

Monographs on

- Insulins (0838, 1637, 1638)

- G-CSF (2206)

- GM-CSF (1641)

- Erythropoietin (1316)

- Interferon gamma (1440)

- Bovine serum (2262)

- Trypsin (0694)

=> Need for requirements specific to raw material


Caution: these requirements for substances used as APIsmight not be adapted to raw materials.

RCG WP

2012 JunePh. Eur. Commission

establishedRaw Materials

for the Production of Cellular and Gene Transfer Products

Working Party

14 experts from Member States+ 1 EMA representative + 1 observer

Survey to National

Pharmacopoeia Authorities

2012 DecemberEDQM / EMA Symposium

2013 AprilInternational Symposium

With manufacturers, regulators and users

General Chapter 5.2.12 Initial phasesRaw materials of biological origin for the production of cell-based and gene therapy medicinal products


Cooperation between EDQM and EMA

User’s needs identified

Classes of raw materials defined

Current variable practices to be harmonised

03/02/2017

5

General Chapter 5.2.12 AimRaw materials of biological origin for the production of cell-based and gene therapy medicinal products

Overarching general chapter covers the quality requirements of raw materials of biological origin used for the production of cell-based and gene therapy products:

• For information / Purpose is not to increase regulation

• To harmonize variable practices

• To identify the critical quality attributes of raw materials

• To encourage raw materials manufacturers

• to provide consistent, predefined quality

• to record and share information on the origin and quality of the raw material

• To help users to manage batch-to-batch variations and changes in raw materials


General Chapter 5.2.12 Final phasesRaw materials of biological origin for the production of cell-based and gene therapy medicinal products


Public consultation Final version preparation

Publication Ph. Eur. 9th Edition

Pharmeuropa(Issue 26.4: Q4 2014 – Q1 2015)

Comments received during public consultation were evaluated

Implementation date:1 January 2017

03/02/2017

6

General Chapter 5.2.12 OverviewRaw materials of biological origin for the production of cell-based and gene therapy medicinal products


1. Scope

Applies to raw materials of biological origin

Raw materials are used for manufacturing or extracting the active substance(s) but are not intended to form part of the active substance

Applies to:

- sera and serum replacement;

- proteins produced by recombinant DNA technology;

- proteins extracted from biological materials;

- vectors.

Not in the scope:

- chemically synthesised raw materials: e.g. basal media (purely composed of chemicals);

- Synthetic peptides or polynucleotides;

- medical devices and plastics.



2. Risk Assessment

Evaluation of the impact must be performed by the user

Origin

Risk factor evaluated in relation to the clinical benefit/risk

03/02/2017

7



3. General requirementsOrigin, Production, General quality requirements (ID/Tests/Assay/Ref. Mat-batch), Storage, Labelling

Three categories




Risks to be minimized

Traceability

Donation <-> final product

03/02/2017

8




Suitable quality management system




Suitable quality management system

Production process

Sterility or known microbial contamination

Additives

03/02/2017

9







03/02/2017

10







03/02/2017

11



4. Sera and serum replacements4.1 Definition / 4.2 Production / 4.3 Identification / 4.4 Tests / 4.5 Assay

Typically complex biological mixtures




03/02/2017

12







03/02/2017

13



5. Proteins produced by recombinant DNA technology5.1 Definition / 5.2 Production / 5.3 Identification / 5.4 Tests / 5.5 Assay

e.g. growth factors, cytokines, hormones, other proteins, mAbs



5. Proteins produced by recombinant DNA technology5.1 Definition / 5.2 Production / 5.3 Identification / 5.4 Tests / 5.5 Assay

03/02/2017

14



6. Proteins extracted from biological material6.1 Definition / 6.2 Production / 6.3 Identification / 6.4 Tests / 6.5 Assay

e.g. enzymes, polyclonal Abs, other proteins (e.g. albumin)




03/02/2017

15






7. Vectors

Usually consideredas starting materials

Reference to general chapter 5.14

03/02/2017

16

Thank you for your attention


Acknowledgement

- Dr Jaana Vesterinen, Chair of the RGC working Party,

- RCG Working Party Members

general chapter 5.2.12. raw materials of biological origin ... · 03/02/2017 2 general chapter...

Documents